IL274828B2 - Compounds for the treatment of neuromuscular disorders - Google Patents

Compounds for the treatment of neuromuscular disorders

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Publication number
IL274828B2
IL274828B2 IL274828A IL27482820A IL274828B2 IL 274828 B2 IL274828 B2 IL 274828B2 IL 274828 A IL274828 A IL 274828A IL 27482820 A IL27482820 A IL 27482820A IL 274828 B2 IL274828 B2 IL 274828B2
Authority
IL
Israel
Prior art keywords
alkyl
phenoxy
optionally substituted
oxazol
substituents
Prior art date
Application number
IL274828A
Other languages
Hebrew (he)
Other versions
IL274828A (en
IL274828B1 (en
Original Assignee
Nmd Pharma As
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US15/842,823 external-priority patent/US10385028B2/en
Application filed by Nmd Pharma As filed Critical Nmd Pharma As
Publication of IL274828A publication Critical patent/IL274828A/en
Publication of IL274828B1 publication Critical patent/IL274828B1/en
Publication of IL274828B2 publication Critical patent/IL274828B2/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A61K31/423—Oxazoles condensed with carbocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4245—Oxadiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/426—1,3-Thiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/428—Thiazoles condensed with carbocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C07D233/60—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to ring nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/04—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/20—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/24—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
    • C07D277/66—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2 with aromatic rings or ring systems directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/06—1,2,3-Thiadiazoles; Hydrogenated 1,2,3-thiadiazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
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    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/12—Radicals substituted by oxygen atoms
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    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/40—Radicals substituted by oxygen atoms
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    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
    • C07D333/16—Radicals substituted by singly bound hetero atoms other than halogen by oxygen atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
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  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Engineering & Computer Science (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Steroid Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Furan Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Claims (22)

2274828/ Claims
1. A compound of Formula (I): Formula (I) wherein: - R is selected from the group consisting of H, deuterium, F, Cl, Br and I; - R is a 5-membered aromatic heterocycle, wherein each of which may be optionally substituted with one or more, identical or different, substituents R; - R is selected from the group consisting of deuterium, tritium, F, Cl, Br, I, CN, CF3, CCl3, CHF2, CHCl2, CH2F, CH2Cl, OCF 3, OCCl3 and isocyanide; - R is selected from the group consisting of H, deuterium, C1-5 alkyl, C2-alkenyl, C2-5 alkynyl, C3-5 cycloalkyl, C5 cycloalkenyl, each of which may be optionally substituted with one or more, identical or different, substituents R; - R is selected from the group consisting of H, C1-5 alkyl optionally substituted with one or more, identical or different, substituents R, C2-5 alkenyl, C2-alkynyl, C3-6 cycloalkyl optionally substituted with one or more, identical or different, substituents R, phenyl optionally substituted with one or more, identical or different, substituents R and benzyl optionally substituted with one or more, identical or different, substituents R; - R is independently selected from the group consisting of H, deuterium, tritium, F, Cl, Br, I, CN, isocyanide, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-5 cycloalkyl, C5 cycloalkenyl, O-C1-5 alkyl, O-C2-5 alkenyl, O-C2-alkynyl, O-C3-5 cycloalkyl, O-C5 cycloalkenyl, -C(=O)-C1-5 alkyl, -C(=O)- 25 2274828/ C2-5 alkenyl, -C(=O)-C2-5 alkynyl, -C(=O)-C3-5 cycloalkyl, -CH2-O-C1-3 alkyl and -CH2-S-C1-3 alkyl, and wherein C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-5 cycloalkyl, C5 cycloalkenyl, O-C1-5 alkyl, O-C2-5 alkenyl, O-C2-alkynyl, O-C3-5 cycloalkyl, O-C5 cycloalkenyl, -C(=O)-C1-5 alkyl, -C(=O)-C2-5 alkenyl, -C(=O)-C2-5 alkynyl, -C(=O)-C3-5 cycloalkyl, -CH2-O-C1-3 alkyl and -CH2-S-C1-3 alkyl may be optionally substituted with one or more halogens; - R is independently selected from the group consisting of deuterium, tritium, F, Cl, Br, I, CN, isocyanide, O-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R, S-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R, CH2-O-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R and CH2-S-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R; - R is independently selected from the group consisting of deuterium and F; - R is independently selected from the group consisting of deuterium, methoxy, nitro, cyano, Cl, Br, I and F; and - n is an integer 0, 1, 2 or 3; or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, with the proviso that when R is F, Cl or Br, R is 1,2-oxazol-5-yl, R is H, R is H and R is H then n is 1, 2 or 3; for use in treating, ameliorating and/or preventing a neuromuscular disorder, and/or for use in reversing and/or ameliorating a neuromuscular blockade.
2. The compound for use according claim 1, wherein R is selected from the group consisting of 1,2-oxazol-3-yl, 1,2-oxazol-4-yl, 1,2-oxazol-5-yl, 1,3-oxazol-2-yl, 1,3-oxazol-4-yl, 1,3-oxazol-5-yl, 1,2-thiazol-3-yl, 1,2-thiazol-4-yl, 1,2-thiazol-5-yl, 1,3-thiazol-2-yl, 1,3-thiazol-4-yl, 1,3-thiazol-5-yl, 1,2,3-thiadiazol-4-yl, 1,2,3-thiadiazol-5-yl, 1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl, 1,3,4-thiadiazol-2-yl, 1,2,5- thiadiazol-3-yl, 1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl and 1,2,5-oxadiazol-3-yl each of which may be optionally substituted with one or more, identical or different, substituents R. 2274828/
3. The compound for use according to any one of claims 1 to 2, wherein the compound is of Formula (II): Formula (II) wherein: - R is selected from the group consisting of H, deuterium, F, Cl, Br and I; - R is selected from the group consisting of deuterium, tritium, F, Cl, Br, I, CN, CF3, CCl3, CHF2, CHCl2, CH2F, CH2Cl, OCF 3, OCCl3 and isocyanide; - R is selected from the group consisting of H, deuterium, C1-5 alkyl, C2-alkenyl, C2-5 alkynyl, C3-5 cycloalkyl, C5 cycloalkenyl, each of which may be optionally substituted with one or more, identical or different, substituents R; - R is selected from the group consisting of H, C1-5 alkyl optionally substituted with one or more, identical or different, substituents R, C2-5 alkenyl, C2-alkynyl, C3-6 cycloalkyl optionally substituted with one or more, identical or different, substituents R, phenyl optionally substituted with one or more, identical or different, substituents R and benzyl optionally substituted with one or more, identical or different, substituents R; - R is independently selected from the group consisting of H, deuterium, tritium, F, Cl, Br, I, CN, isocyanide, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-5 cycloalkyl, C5 cycloalkenyl, O-C1-5 alkyl, O-C2-5 alkenyl, O-C2-alkynyl, O-C3-5 cycloalkyl, O-C5 cycloalkenyl, -C(=O)-C1-5 alkyl, -C(=O)-C2-5 alkenyl, -C(=O)-C2-5 alkynyl, -C(=O)-C3-5 cycloalkyl, -CH2-O-C1-3 alkyl and -CH2-S-C1-3 alkyl, and wherein C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-5 cycloalkyl, C5 cycloalkenyl, O-C1-5 alkyl, O-C2-5 alkenyl, O-C2-5 alkynyl, O-C3-5 cycloalkyl, O-C5 cycloalkenyl, -C(=O)-C1-5 alkyl, -C(=O)-C2-5 alkenyl, -C(=O)-C2-5 alkynyl, -C(=O)-C3-5 cycloalkyl, -CH2-O-C1-3 alkyl 2274828/ and -CH2-S-C1-3 alkyl may be optionally substituted with one or more halogens; - R is independently selected from the group consisting of deuterium, tritium, F, Cl, Br, I, CN, isocyanide, O-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R, S-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R, CH2-O-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R and CH2-S-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R; - R is independently selected from the group consisting of deuterium and F; - R is independently selected from the group consisting of deuterium, methoxy, nitro, cyano, Cl, Br, I and F, - m is an integer 0, 1 or 2; and - n is an integer 0, 1, 2 or 3.
4. The compound for use according to any one of claims 1 to 2, wherein the compound is of Formula (III): Formula (III) wherein: - R is selected from the group consisting of H, deuterium, F, Cl, Br and I; - R is selected from the group consisting of deuterium, tritium, F, Cl, Br, I, CN, CF3, CCl3, CHF2, CHCl2, CH2F, CH2Cl, OCF 3, OCCl3 and isocyanide; - R is selected from the group consisting of H, deuterium, C1-5 alkyl, C2-alkenyl, C2-5 alkynyl, C3-5 cycloalkyl, C5 cycloalkenyl, each of which may be optionally substituted with one or more, identical or different, substituents R; 2274828/ - R is selected from the group consisting of H, C1-5 alkyl optionally substituted with one or more, identical or different, substituents R, C2-5 alkenyl, C2-alkynyl, C3-6 cycloalkyl optionally substituted with one or more, identical or different, substituents R, phenyl optionally substituted with one or more, identical or different, substituents R and benzyl optionally substituted with one or more, identical or different, substituents R; - R is independently selected from the group consisting of H, deuterium, tritium, F, Cl, Br, I, CN, isocyanide, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-5 cycloalkyl, C5 cycloalkenyl, O-C1-5 alkyl, O-C2-5 alkenyl, O-C2-alkynyl, O-C3-5 cycloalkyl, O-C5 cycloalkenyl, -C(=O)-C1-5 alkyl, -C(=O)- C2-5 alkenyl, -C(=O)-C2-5 alkynyl, -C(=O)-C3-5 cycloalkyl, -CH2-O-C1-3 alkyl and -CH2-S-C1-3 alkyl, and wherein C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-5 cycloalkyl, C5 cycloalkenyl, O-C1-5 alkyl, O-C2-5 alkenyl, O-C2-alkynyl, O-C3-5 cycloalkyl, O-C5 cycloalkenyl, -C(=O)-C1-5 alkyl, -C(=O)-C2-5 alkenyl, -C(=O)-C2-5 alkynyl, -C(=O)-C3-5 cycloalkyl, -CH2-O-C1-3 alkyl and -CH2-S-C1-3 alkyl may be optionally substituted with one or more halogens; - R is independently selected from the group consisting of deuterium, tritium, F, Cl, Br, I, CN, isocyanide, O-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R, S-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R, CH2-O-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R and CH2-S-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R; - R is independently selected from the group consisting of deuterium and F; - R is independently selected from the group consisting of deuterium, methoxy, nitro, cyano, Cl, Br, I and F; - m is an integer 0, 1 or 2; and - n is an integer 0, 1, 2 or 3.
5. The compound for use according to any one of claims 1 to 2, wherein the compound is of Formula (XVI): 2274828/ Formula (XVI) wherein: - R is selected from the group consisting of H, deuterium, F, Cl, Br and I; - R is selected from the group consisting of deuterium, tritium, F, Cl, Br, I, CN, CF3, CCl3, CHF2, CHCl2, CH2F, CH2Cl, OCF 3, OCCl3 and isocyanide; - R is selected from the group consisting of C1-5 alkyl, C2-5 alkenyl, C2-alkynyl, C3-5 cycloalkyl, C5 cycloalkenyl, each of which may be optionally substituted with one or more, identical or different, substituents R; - R is selected from the group consisting of H, C1-5 alkyl optionally substituted with one or more, identical or different, substituents R, C2-5 alkenyl, C2-alkynyl, C3-6 cycloalkyl optionally substituted with one or more, identical or different, substituents R, phenyl optionally substituted with one or more, identical or different, substituents R and benzyl optionally substituted with one or more, identical or different, substituents R; - R is independently selected from the group consisting of H, deuterium, tritium, F, Cl, Br, I, CN, isocyanide, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-5 cycloalkyl, C5 cycloalkenyl, O-C1-5 alkyl, O-C2-5 alkenyl, O-C2-alkynyl, O-C3-5 cycloalkyl, O-C5 cycloalkenyl, -C(=O)-C1-5 alkyl, -C(=O)-C2-5 alkenyl, -C(=O)-C2-5 alkynyl, -C(=O)-C3-5 cycloalkyl, -CH2-O-C1-3 alkyl and -CH2-S-C1-3 alkyl, and wherein C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-5 cycloalkyl, C5 cycloalkenyl, O-C1-5 alkyl, O-C2-5 alkenyl, O-C2-alkynyl, O-C3-5 cycloalkyl, O-C5 cycloalkenyl, -C(=O)-C1-5 alkyl, -C(=O)-C2-5 alkenyl, -C(=O)-C2-5 alkynyl, -C(=O)-C3-5 cycloalkyl, -CH2-O-C1-3 alkyl and -CH2-S-C1-3 alkyl may be optionally substituted with one or more halogens; 2274828/ - R is independently selected from the group consisting of deuterium, tritium, F, Cl, Br, I, CN, isocyanide, O-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R, S-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R, CH2-O-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R and CH2-S-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R; - R is independently selected from the group consisting of deuterium and F; - R is independently selected from the group consisting of deuterium, methoxy, nitro, cyano, Cl, Br, I and F; - m is an integer 0, 1 or 2; and - n is an integer 0, 1, 2 or 3.
6. The compound for use according to any one of claims 1 to 2, wherein the compound is of Formula (XVII): Formula (XVII) wherein: - R is selected from the group consisting of H, deuterium, F, Cl, Br and I; - R is selected from the group consisting of deuterium, tritium, F, Cl, Br, I, CN, CF3, CCl3, CHF2, CHCl2, CH2F, CH2Cl, OCF 3, OCCl3 and isocyanide; - R is selected from the group consisting of C1-5 alkyl, C2-5 alkenyl, C2-alkynyl, C3-5 cycloalkyl, C5 cycloalkenyl, each of which may be optionally substituted with one or more, identical or different, substituents R; - R is selected from the group consisting of H, C1-5 alkyl optionally substituted with one or more, identical or different, substituents R, C2-5 alkenyl, C2-5 alkynyl, C3-6 cycloalkyl optionally substituted with one or more, identical 2274828/ or different, substituents R, phenyl optionally substituted with one or more, identical or different, substituents R and benzyl optionally substituted with one or more, identical or different, substituents R; - R is independently selected from the group consisting of H, deuterium, tritium, F, Cl, Br, I, CN, isocyanide, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-5 cycloalkyl, C5 cycloalkenyl, O-C1-5 alkyl, O-C2-5 alkenyl, O-C2-alkynyl, O-C3-5 cycloalkyl, O-C5 cycloalkenyl, -C(=O)-C1-5 alkyl, -C(=O)-C2-5 alkenyl, -C(=O)-C2-5 alkynyl, -C(=O)-C3-5 cycloalkyl, -CH2-O-C1-3 alkyl and -CH2-S-C1-3 alkyl, and wherein C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-5 cycloalkyl, C5 cycloalkenyl, O-C1-5 alkyl, O-C2-5 alkenyl, O-C2-5 alkynyl, O-C3-5 cycloalkyl, O-C5 cycloalkenyl, -C(=O)-C1-5 alkyl, -C(=O)-C2-5 alkenyl, -C(=O)-C2-5 alkynyl, -C(=O)-C3-5 cycloalkyl, -CH2-O-C1-3 alkyl and -CH2-S-C1-3 alkyl may be optionally substituted with one or more halogens; - R is independently selected from the group consisting of deuterium, tritium, F, Cl, Br, I, CN, isocyanide, O-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R, S-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R, CH2-O-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R and CH2-S-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R; - R is independently selected from the group consisting of deuterium and F; - R is independently selected from the group consisting of deuterium, methoxy, nitro, cyano, Cl, Br, I and F; - m is an integer 0 or 1; and - n is an integer 0, 1, 2 or 3.
7. The compound for use according to any of claims 1 to 6, wherein n is 0 or 1.
8. The compound for use according to any one of claims 1 to 7, wherein R is C1-alkyl optionally substituted with one or more, identical or different, substituents R or C1-5 cycloalkyl optionally substituted with one or more, identical or different, substituents R.
9. The compound for use according to any one of claims 1 to 8, wherein R is selected from the group consisting of F, Cl, Br and I. 2274828/
10. The compound for use according to any one of claims 1 to 9, wherein R is hydrogen.
11. The compound for use according to any one of claims 3 to 10, wherein m is 0.
12. The compound for use according to any one of claims 1 to 11, wherein the compound is an inhibitor of the ClC-1 ion channel.
13. The compound for use according to any one of claims 1 to 12, wherein the neuromuscular disorder is selected from the group consisting of myasthenia gravis, amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), critical illness myopathy (CIM), Charcot-Marie tooth disease (CMT) and sarcopenia.
14. The compound for use according to any one of claims 1 to 13, wherein the neuromuscular disorder has been induced by a neuromuscular blocking agent.
15. A compound of Formula (I): Formula (I) wherein: - R is selected from the group consisting of F, Cl, Br and I; - R is a 5-membered aromatic heterocycle, wherein each of which may be optionally substituted with one or more, identical or different, substituents R - R is selected from the group consisting of deuterium, tritium, F, Cl, Br, I, CN, CF3, CCl3, CHF2, CHCl2, CH2F, CH2Cl, OCF 3, OCCl3 and isocyanide; - R is selected from the group consisting of H, deuterium, C1-5 alkyl, C2-alkenyl, C2-5 alkynyl, C3-5 cycloalkyl, C5 cycloalkenyl, each of which may 2274828/ be optionally substituted with one or more, identical or different, substituents R; - R is selected from the group consisting of H, C1-5 alkyl optionally substituted with one or more, identical or different, substituents R, C2-5 alkenyl, C2-alkynyl, C3-6 cycloalkyl optionally substituted with one or more, identical or different, substituents R, phenyl optionally substituted with one or more, identical or different, substituents R and benzyl optionally substituted with one or more, identical or different, substituents R; - R is independently selected from the group consisting of H, deuterium, tritium, F, Cl, Br, I, CN, isocyanide, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-5 cycloalkyl, C5 cycloalkenyl, O-C1-5 alkyl, O-C2-5 alkenyl, O-C2-alkynyl, O-C3-5 cycloalkyl, O-C5 cycloalkenyl, -C(=O)-C1-5 alkyl, -C(=O)-C2-5 alkenyl, -C(=O)-C2-5 alkynyl, -C(=O)-C3-5 cycloalkyl, -CH2-O-C1-3 alkyl and -CH2-S-C1-3 alkyl, and wherein C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-5 cycloalkyl, C5 cycloalkenyl, O-C1-5 alkyl, O-C2-5 alkenyl, O-C2-5 alkynyl, O-C3-5 cycloalkyl, O-C5 cycloalkenyl, -C(=O)-C1-5 alkyl, -C(=O)-C2-5 alkenyl, -C(=O)-C2-5 alkynyl, -C(=O)-C3-5 cycloalkyl, -CH2-O-C1-3 alkyl and -CH2-S-C1-3 alkyl may be optionally substituted with one or more halogens; - R is independently selected from the group consisting of deuterium, tritium, F, Cl, Br, I, CN, isocyanide, O-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R, S-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R, CH2-O-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R and CH2-S-C1-3 alkyl optionally substituted with one or more, identical or different, substituents R; - R is independently selected from the group consisting of deuterium and F; - R is independently selected from the group consisting of deuterium, methoxy, nitro, cyano, Cl, Br, I and F; and - n is an integer 0, 1, 2 or 3; or a pharmaceutically acceptable salt, hydrate, polymorph, tautomer, or solvate thereof, with the proviso that when R is H then R is 1,2,3-thiadiazol-4-yl, 1,3,4-thiadiazol-2-yl, 1,2-thiazol-3-yl, 1,2-oxazol-3-yl or 1,3-oxazol-4-yl.
16. The compound according to claim 15, wherein R is Cl or Br. 35 2274828/
17. The compound according to any one of claims 15 to 16, wherein R is selected from the group consisting of 1,2,3-thiadiazol-4-yl, 1,3,4-thiadiazol-2-yl, 1,2-thiazol-3-yl, 1,2-oxazol-3-yl, 1,2-oxazol-5-yl and 1,3-oxazol-4-yl each of which may be optionally substituted with one or more, identical or different, substituents R.
18. The compound according to any one of claims 15 to 17, wherein R is C1-5 alkyl optionally substituted with one or more, identical or different, substituents R or C1-5 cycloalkyl optionally substituted with one or more, identical or different, substituents R.
19. The compound according to any one of claims 15 to 17, wherein R is H or deuterium.
20. The compound according to any one of claims 15 to 19, wherein R is hydrogen.
21. The compound according to any of claims 15 to 21, wherein n is 0 or 1.
22. The compound according to any of claims 15 to 22, wherein the compound is selected from the group consisting of: (2S)-2-[4-bromo-2-(1,2-oxazol-5-yl)phenoxy]butanoic acid; (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]butanoic acid; (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]-3-methylbutanoic acid; (2S)-2-{4-bromo-2-[3-(propan-2-yl)-1,2-oxazol-5-yl]phenoxy}propanoic acid; (2S)-2-[4-bromo-2-(4-methyl-1,2-oxazol-3-yl)phenoxy]propanoic acid; (2S)-2-[4-bromo-2-chloro-6-(1,2-oxazol-3-yl)phenoxy]propanoic acid; (2S)-2-[4-bromo-2-(5-methyl-1,2-oxazol-3-yl)phenoxy]propanoic acid; (2S)-2-[4-chloro-2-(3-methyl-1,2,4-oxadiazol-5-yl)phenoxy]propanoic acid; (2S)-2-[4-bromo-2-(5-cyclopropyl-1,2-oxazol-3-yl)phenoxy]propanoic acid; (2S)-2-[4-chloro-2-(1,3-thiazol-2-yl)phenoxy]propanoic acid; (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; (2S)-2-[4-bromo-2-(3-methyl-1,2-oxazol-5-yl)phenoxy]propanoic acid; (2S)-2-[4-bromo-2-(1H-imidazol-2-yl)phenoxy]propanoic acid; (2S)-2-[4-bromo-2-(1H-imidazol-4-yl)phenoxy]propanoic acid; (2R)-2-[4-bromo-2-(1,2-oxazol-5-yl)phenoxy]-3-fluoropropanoic acid; (2S)-2-[4-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)phenoxy]propanoic acid; (2S)-2-[4-chloro-2-(1H-pyrazol-3-yl)phenoxy]propanoic acid; 2274828/ (2S)-2-[4-chloro-2-(thiophen-2-yl)phenoxy]propanoic acid; (2S)-2-[4-chloro-2-(1,2-oxazol-5-yl)phenoxy]propanoic acid; (2S)-2-[4-chloro-2-(1-methyl-1H-pyrazol-4-yl)phenoxy]propanoic acid; (2S)-2-[4-bromo-2-(1,3,4-oxadiazol-2-yl)phenoxy]propanoic acid; (2S)-2-[4-bromo-2-(1,2-oxazol-5-yl)phenoxy]propanoic acid; (2S)-2-[4-chloro-2-(1H-pyrazol-1-yl)phenoxy]propanoic acid; (2S)-2-[4,5-dichloro-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; (2S)-2-[4-bromo-5-fluoro-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; (2S)-2-[4-chloro-5-fluoro-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; (2S)-2-[4-bromo-2-(1,3-oxazol-4-yl)phenoxy]propanoic acid; (2S)-2-[4-chloro-2-(1,2-oxazol-3-yl)phenoxy]-3-cyclopropylpropanoic acid; (2S)-2-[4-fluoro-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; (2R)-2-[4-chloro-2-(1,2-oxazol-3-yl)phenoxy]-3-fluoropropanoic acid; (2S)-2-[4-chloro-2-(4-methyl-1,2-oxazol-3-yl)phenoxy]propanoic acid; (2S)-2-[4-chloro-2-(5-cyclopropyl-1,2-oxazol-3-yl)phenoxy]propanoic acid; (2S)-2-[4-chloro-2-(1,2-oxazol-3-yl)phenoxy]-3-methylbutanoic acid; (2S)-2-[4-chloro-2-(1,2-oxazol-3-yl)phenoxy]butanoic acid; (2S)-2-[4-chloro-2-(1,2-oxazol-3-yl)phenoxy]propanoic acid; (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]-3-cyclopropylpropanoic acid; (2S)-2-[4-chloro-2-(1,3-oxazol-2-yl)phenoxy]propanoic acid; (2R)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]-3-fluoropropanoic acid; (2S)-2-[4-bromo-2-(2H-1,2,3-triazol-4-yl)phenoxy]propanoic acid; (2S)-2-[4-bromo-5-fluoro-2-(1,2-oxazol-3-yl)phenoxy]-4-fluorobutanoic acid; (2S)-2-[4-bromo-2-(1,2,3-thiadiazol-4-yl)phenoxy]propanoic acid; (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]-4-fluorobutanoic acid; (2R)-2-[4-chloro-5-fluoro-2-(1,2-oxazol-5-yl)phenoxy]-3-fluoropropanoic acid; (2S)-2-[4-bromo-2-(1,3-thiazol-4-yl)phenoxy]propanoic acid; (2S)-2-[4-bromo-5-fluoro-2-(1,3-oxazol-4-yl)phenoxy]propanoic acid; (2S)-2-[4-chloro-2-(1,2-oxazol-5-yl)phenoxy]-3-methylbutanoic acid; (2S)-2-[4-chloro-2-(1,2-oxazol-5-yl)phenoxy]-3-cyclopropylpropanoic acid; (2R)-2-[4-chloro-2-(1,2-oxazol-5-yl)phenoxy]-3-fluoropropanoic acid; (2S)-2-[4-chloro-5-fluoro-2-(1,2-oxazol-5-yl)phenoxy]propanoic acid; (2S)-2-[4-chloro-2-(1,2-oxazol-5-yl)phenoxy]butanoic acid; (2S)-2-[4-bromo-2-(1,2-oxazol-4-yl)phenoxy]propanoic acid; (2R)-2-[4-chloro-5-fluoro-2-(1,2-oxazol-3-yl)phenoxy]-3-fluoropropanoic acid; 35 2274828/ (2S)-2-[4-chloro-2-(1,3-oxazol-4-yl)phenoxy]propanoic acid; 2-[4-bromo-2-(1,2,3-thiadiazol-4-yl)phenoxy]acetic acid; (2S)-2-[4-bromo-2-(1,2-oxazol-5-yl)phenoxy]-2-cyclopropylacetic acid; (2S)-2-[4-bromo-5-fluoro-2-(1,2-oxazol-3-yl)phenoxy]-2-cyclopropylacetic acid; (2S)-2-[4-bromo-2-(1,2,3-thiadiazol-4-yl)phenoxy]-3-cyclopropylpropanoic acid; 2-[4-bromo-2-(4-methyl-1,2-oxazol-3-yl)phenoxy]acetic acid; (2S)-2-[4-bromo-5-fluoro-2-(1,2-oxazol-5-yl)phenoxy]propanoic acid; (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]-3-cyclobutylpropanoic acid; (2S)-2-[4-bromo-5-fluoro-2-(1,2,3-thiadiazol-4-yl)phenoxy]propanoic acid; 2-[4-bromo-5-fluoro-2-(1,2-oxazol-3-yl)phenoxy]acetic acid; (2S)-2-[4-bromo-2-(1,2,3-thiadiazol-4-yl)phenoxy]butanoic acid; (2R)-2-[4-bromo-2-(1,2,3-thiadiazol-4-yl)phenoxy]-3-fluoropropanoic acid; (2S)-2-[4-bromo-2-(1,3,4-thiadiazol-2-yl)phenoxy]propanoic acid; 2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]acetic acid; (2R)-2-[4-bromo-5-fluoro-2-(1,2-oxazol-3-yl)phenoxy]-3-fluoropropanoic acid; (2S)-2-[4-chloro-2-(1,2,3-thiadiazol-4-yl)phenoxy]propanoic acid; (2S)-2-[4-bromo-2-(1,3-oxazol-5-yl)phenoxy]propanoic acid; (2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]-3-ethoxypropanoic acid; 2-[4-bromo-2-(1,3-oxazol-4-yl)phenoxy]acetic acid; and (2S)-2-[4-chloro-2-(1,2-thiazol-3-yl)phenoxy]propanoic acid.
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